Tumour Markers in Bladder Cancer

Introduction

Bladder cancer is the fourth most common type of cancer among men and the eighth most common among women. Each year more than 50,000 and 24,000 new bladder cancers are diagnosed in the US and in Germany, respectively.1,2 Patients with bladder cancer are treated for painless microhaematuria or gross haematuria in the absence of urinary tract infection (UTI) and/or irritative voiding symptoms.
The gold standard for detecting bladder cancer is cystoscopy. Cystoscopy is a reliable investigation that identifies nearly all papillary and sessile lesions. It is an invasive procedure causing some discomfort for patients. At initial diagnosis, 65% to 70% of bladder cancers are confined to the urothelium (Ta, Tis) or invade the lamina propria (T1) and can be managed with endoscopic resection and intravesical therapy. Thirty per cent to 35% of newly diagnosed bladder cancers have invaded the detrusor muscle (T2–T4).3–5 Ta, grade 1 and grade 2 tumours recur in 30% to 70% and progress to muscle-invasive disease in less than 7% of patients. In contrast, high-grade stage T1 tumours have a progression rate of 30% to 50%.3–5 The high recurrence rate and the risk of progression necessitate follow-up care after treatment for bladder cancer at regular intervals. Follow-up protocols include cystoscopy every three months for one to two years, every six months for an additional two to three years and then annually.
To improve early detection of bladder cancer, as well as to monitor treatment response and tumour recurrence, bladder tumour markers are critical. An ideal bladder cancer test would be non-invasive, highly sensitive and specific, inexpensive, easy to perform and yield highly reproducible results.6 The validity of a tumour marker test can be expressed as sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Sensitivity and specificity are terms in statistics for the probability of the identification of those with or without the condition (bladder cancer). PPV and NPV are terms for the probability of the usefulness of a test in identifying true positives or true negatives. Definitions of these are shown in Figure 1. An accurate tumour marker also would have the potential to replace or delay cystoscopy in the follow-up of bladder cancer patients. If the test for a bladder cancer marker accomplished these criteria, this would improve the quality of life of patients and decrease the cost of surveillance by substituting a less expensive test for a more expensive procedure.7